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Metals and Metal Ions in Human Health, Diseases, and Environment

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 August 2026 | Viewed by 11132

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Dr. Agnieszka Scibior

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Department of Biomedicine and Environmental Research, Faculty of Medicine, The John Paul II Catholic University of Lublin, Konstantynów 1J, 20-708 Lublin, Poland
Interests: elements; metal interactions; mechanisms of metal toxicity
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Prof. Dr. Juan Llopis

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Department of Physiology, Institute of Nutrition and Food Technology, Biomedical Research Center, Institute of Biosanitary Research, University of Granada, 18071 Granada, Spain
Interests: nutrition; micronutrients; metals; nanoparticles
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Prof. Dr. Manuel Aureliano

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Department of Biological Sciences and Biotechnology, University of Algarve, Faro, Portugal
Interests: metals in molecular sciences; decavanadate biochemistry; polyoxometalate (POM) interactions with proteins; metals and biomedical applications
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Special Issue Information

Dear Colleagues,

Chemical elements (micro- and macro-elements)/metal ions play a crucial role in human health, as they are essential for the proper functioning of the organism. Maintaining a balanced diet rich in their various sources is essential to sustaining good health and preventing many diseases. In some cases, however, it may be necessary to supplement their deficiencies with supplements.

Chemical elements play a crucial role in medicine, both in the diagnosis and treatment of certain diseases. For example, calcium (Ca) is used in the treatment of osteoporosis, sodium (Na) and potassium (K) are part of the treatment of cardiovascular diseases and electrolyte imbalance disorders, iron (Fe) and copper (Cu) are employed in the treatment of anemia. In turn, zinc (Zn) is used in the treatment of colds and other infections and magnesium (Mg) is part of the treatment of migraines and other conditions. Moreover, lithium (Li) as an antidepressant, vanadium (V) as an antidiabetic, constitutes examples of the importance of metals in biology and medicine. Currently, selenium (Se) is being studied for its potential benefits in cancer diseases. Furthermore, radium (Ra) and other radioactive isotopes are used in cancer therapy (radiotherapy) and medical diagnostics, e.g., in positron emission tomography.

It should be mentioned that elements in the environment have a significant impact on human health. They can accumulate in the body and lead to long-term health effects. The increasing levels of metal concentration in recent years are one of the most burdensome aspects of environmental pollution. The permanent nature of metal contamination is dangerous as well as their incorporation into the food chain. The effects of their actions often become evident after many years and are not fully understood. Therefore, proper management of the presence of metals, monitoring of environmental quality, and limitation of emissions are crucial for public health protection and maintaining ecological balance.

We invite authors to submit original research papers or review articles on the role of toxic and essential metals/metal ions in human health and diseases. We also accept studies and review papers about the mechanisms of action and toxicity of elements. Moreover, we accept original papers or review articles on metals in the environment and their impact on human health with a focus on therapeutic insights to counteract the toxicity.

Potential topics include, but are not limited to the following:

Unique biological effects of metals in diseases
Human exposure to metals
Innovative methods/promising strategies for assessing metals toxicity
Perspectives on the safety evaluation of metals
Metals, metals based complexes and polyoxometalates in modern-day medicine
Metals, metals based complexes and polyoxometalates in cancer effects
Metals, metal-based complexes and polyoxometalates in oxidative stress and lipid peroxidation
Heavy metals in the environment and health impact
Heavy metals in the ecosystem
Current challenges in human health, diseases, and environment and potential directions in further research.

Dr. Agnieszka Scibior
Prof. Dr. Juan Llopis
Prof. Dr. Manuel Aureliano
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

metal toxicity
metal-based drugs
polyoxometalates
protein metalation
human health problems
diseases
in vitro/in vivo studies
human studies
environmental pollution

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Published Papers (7 papers)

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Research

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24 pages, 63998 KB

Open AccessArticle

Hexavalent Chromium Toxicity in the Pancreas: A Study on the Protective Effects of Hypericum perforatum Extract

by Jelena Savici, Simona Marc, Oana-Maria Boldura, Catalin Cicerone Grigorescu, Cristina Paul, Cristina Văduva and Diana Brezovan

Int. J. Mol. Sci. 2026, 27(8), 3706; https://doi.org/10.3390/ijms27083706 - 21 Apr 2026

Viewed by 262

Abstract

Hexavalent chromium, a widespread heavy metal, induces apoptosis via the mitochondrial pathway through Bax (pro-apoptotic) and Bcl2 (anti-apoptotic) proteins. Hypericum perforatum, rich in antioxidants, can neutralise free radicals. This study investigated the effects of CrVI on the pancreas and the protective role of Hypericum perforatum. Five groups of animals were used: control, Cr (CrVI for 3 months), CrH (CrVI + 2.5% Hypericum perforatum extract made from flowers, for 3 months), Cr2 (CrVI for 3 months + distilled water for 1 month), and CrH2 (CrVI for 3 months + Hypericum perforatum extract for 1 month). Samples were collected for histological analysis, gene expression (qRT-PCR), and blood glucose level analysis. CrVI exposure (Cr, Cr2) caused pancreatic damage: oedema, reduced islet size, endocrine cell vacuolisation, and endothelial swelling. Lesions were milder in CrH, while CrH2 resembled the control group. The Bax/Bcl2 ratio increased under CrVI (highest in Cr2), indicating apoptosis, but decreased toward control values in CrH and CrH2. Blood glucose levels confirmed these findings. CrVI proved toxic to the endocrine pancreas, inducing structural and molecular alterations that impaired carbohydrate metabolism. Administration of Hypericum perforatum extract reduced these effects, confirming its antioxidant action and potential as a protective agent against CrVI-induced oxidative stress. Full article

(This article belongs to the Special Issue Metals and Metal Ions in Human Health, Diseases, and Environment)

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18 pages, 2989 KB

Open AccessArticle

Neurotoxic Effect of Manganese and Vanadium Co-Exposure in Animal Models of Parkinson’s Disease

by Alejandra Bargues-Carot, Naveen Kondru, Maddlyn Haller, Gary Zenitsky, Huajun Jin, Vellareddy Anantharam, Arthi Kanthasamy and Anumantha G. Kanthasamy

Int. J. Mol. Sci. 2026, 27(4), 1757; https://doi.org/10.3390/ijms27041757 - 12 Feb 2026

Viewed by 469

Abstract

Chronic environmental exposure to mixtures of heavy metals like manganese (Mn) and vanadium (V) has been associated with Parkinson’s disease (PD). We investigated the poorly understood neurotoxic effects of Mn/V co-exposure on PD-relevant behavioral phenotypes in transgenic mice expressing the human alpha-synuclein (αSyn) A53T mutant. C57BL/6 wild-type (WT) and transgenic A53T mice were intranasally co-exposed to 100 µg MnCl₂ and 75 µg V₂O₅ five times weekly for three months, simulating a 5-day workweek. This led to significant Mn/V accumulation in the brain. Exploratory locomotor activity declined significantly in Mn/V-treated A53T mice, but not in Mn/V-treated WT mice when compared to their respective vehicle controls. Motor coordination, assessed via a forced locomotor activity test, was not significantly affected in either group. In Mn/V-treated A53T mice, olfactory deficits were present, but not in Mn/V-treated WT mice. Behavioral despair, assessed by tail suspension and forced swim tests, was not induced by Mn/V co-exposure in any group compared to their vehicle controls. Mn/V-treated A53T mice exhibited anxiety-like behavior and hyperactivity. These findings suggest that Mn/V co-exposure exacerbates neurotoxic effects in A53T mice, with a more pronounced effect in males, providing insight into the role of metal mixture exposure in environmentally linked Parkinsonism. Full article

(This article belongs to the Special Issue Metals and Metal Ions in Human Health, Diseases, and Environment)

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15 pages, 6285 KB

Open AccessArticle

Is Zinc Accumulation Increased in Hyperplastic Compared to Normal Prostate Tissue

by Tomislav Pejčić, Biljana Dojčinović, Milica Zeković, Uroš Bumbaširević, Tomislav Tosti, Živoslav Tešić, Lato Pezo, Darko Jovanović, Darko Laketić and Milica Kalaba

Int. J. Mol. Sci. 2026, 27(3), 1466; https://doi.org/10.3390/ijms27031466 - 2 Feb 2026

Viewed by 682

Abstract

In the male body, zinc accumulates most abundantly in prostatic cells, where it plays a key role in producing high amounts of citrate in seminal fluid. Intraprostatic accumulation of Zn increases during the development of benign prostatic hyperplasia (BPH), one of the most common diseases in men over 50 years of age. Continuing our investigations on intraprostatic androgens, in this study, we analyzed the mineral content (Zn, Ca, Cu, K, Mg, Mn, and Na) in the transitional zone (TZ) of the prostate using inductively coupled plasma optical emission spectrometry (ICP-OES). The concentrations of testosterone (T) and dihydrotestosterone (DHT) were determined by liquid chromatography–mass spectrometry (LC-MS). Group-wise and correlation analyses demonstrated a descriptive trend toward a volume-dependent increase in Zn concentrations within TZ tissue, whereas other elements exhibited heterogeneous covariance patterns; intraprostatic hormone levels, although elevated in larger prostates, showed no consistent linear correlations with elemental concentrations. Given the observational design of the present study, the reported tissue Zn profiles cannot be interpreted as evidence supporting supplementation in BPH, and any potential clinical implications warrant evaluation in rigorously designed interventional studies. Full article

(This article belongs to the Special Issue Metals and Metal Ions in Human Health, Diseases, and Environment)

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24 pages, 2618 KB

Open AccessArticle

Metal-Associated Particulate Matter (PM_2.5) Induces Cognitive Dysfunction: Polygonum multiflorum Improves Neuroinflammation and Synaptic Function

by Hye Ji Choi, Hyo Lim Lee and Ho Jin Heo

Int. J. Mol. Sci. 2026, 27(1), 230; https://doi.org/10.3390/ijms27010230 - 25 Dec 2025

Viewed by 861

Abstract

Fine particulate matter (PM_2.5), which contains heavy metals such as Al, Fe, Mg, and Mn, among others, induces cognitive dysfunction through oxidative stress, neuroinflammation, and impaired mitochondria. This study evaluated the neuroprotective effects of a 40% ethanol extract of Polygonum multiflorum (EPM) on PM_2.5-induced cognitive dysfunction in a mouse model. Behavioral assessments demonstrated attenuated learning and memory impairment following EPM treatment. Redox homeostasis was restored through increased expression of superoxide dismutase (SOD) and glutathione (GSH) and decreased levels of malondialdehyde (MDA) and mitochondrial reactive oxygen species (mtROS) in the EPM group. Mitochondrial function was attenuated, as indicated by recovery of mitochondrial membrane potential and ATP levels. EPM inhibited neuroinflammation by downregulating the TLR4-MyD88-NF-κB pathway and maintaining blood–brain barrier integrity through the upregulation of tight junction proteins. It modulated neuronal apoptosis through the JNK pathway, reducing the accumulation of amyloid-beta and phosphorylated tau. Synaptic plasticity was preserved through upregulation of BDNF/TrkB signaling and cholinergic neurotransmission via regulation of acetylcholine (ACh), acetylcholinesterase (AChE), and choline acetyltransferase (ChAT). To standardize EPM, high-performance liquid chromatography (HPLC) confirmed the presence of the bioactive compound, tetrahydroxystilbene glucoside (TSG). These findings suggest that EPM may be a promising functional food candidate for mitigating PM_2.5-related cognitive impairments. Full article

(This article belongs to the Special Issue Metals and Metal Ions in Human Health, Diseases, and Environment)

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13 pages, 1261 KB

Open AccessArticle

Metallomic Profile of Placental Tissue and Its Association with Maternal and Neonatal Parameters: A Cross-Sectional ICP-OES Study in Lower Silesia

by Aleksandra Kuzan, Emilia Królewicz, Marta Kardach, Justyna Rewak-Soroczyńska, Małgorzata Kowalska, Aldona Molęda and Rafal J. Wiglusz

Int. J. Mol. Sci. 2025, 26(24), 11985; https://doi.org/10.3390/ijms262411985 - 12 Dec 2025

Viewed by 505

Abstract

The placenta, a temporary organ that connects mother and child for nutrient and metabolite exchange, becomes medical waste after birth but can provide valuable metabolic insights. Thirty-three placenta samples were analyzed using ICP-OES to determine concentrations of ten elements, including macro-, micro-, trace, and heavy metals. Results were compared with maternal and neonatal data, including Apgar scores, maternal age, and blood parameters. Correlations were found between elements (e.g., Ca–Mg, Fe–Zn, and Mn–Cu) and between mineral levels and maternal or infant parameters (e.g., Ca–RBC, Mn–Hb, Cu–PLT, and Cu–UA Pi). No quantifiable heavy metals were detected, nor associations with smoking, gestational diabetes, preterm birth, birth weight, or Apgar scores. Findings suggest that maintaining proper blood morphology and preventing anemia in pregnancy requires attention not only to iron but also to Ca²⁺, Mg²⁺, and Mn²⁺ levels. Manganese and copper assessment may be beneficial for diagnostic purposes in pregnant women. Further large-scale tissue studies are recommended, including comprehensive maternal–fetal health data such as Doppler velocimetry of placental vessels. Full article

(This article belongs to the Special Issue Metals and Metal Ions in Human Health, Diseases, and Environment)

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25 pages, 4469 KB

Open AccessArticle

Spirulina and Chlorella Dietary Supplements—Are They a Source Solely of Valuable Nutrients?

by Małgorzata Sochacka, Bartosz Kózka, Eliza Kurek and Joanna Giebułtowicz

Int. J. Mol. Sci. 2025, 26(21), 10468; https://doi.org/10.3390/ijms262110468 - 28 Oct 2025

Cited by 1 | Viewed by 6335

Abstract

Spirulina and Chlorella are nutrient-rich microalgae widely consumed as dietary supplements; however, their high biosorption capacity raises concerns regarding the accumulation of environmental contaminants. This study analyzed 52 commercially available Spirulina and Chlorella products (29 conventional, 23 organic) to assess the co-occurrence of heavy metals and pharmaceutical residues, as these two classes of contaminants represent distinct yet complementary indicators of environmental pollution—heavy metals reflect long-term inputs from natural and industrial sources, while pharmaceuticals signal more recent contamination linked to human activity and wastewater discharge. To the best of our knowledge, this is the first study to investigate the presence of pharmaceutical residues—including cardiovascular drugs, antidepressants, antibiotics, and sulfonamides—in both conventional and organic formulations of microalgae-based dietary supplements. The analyses were performed using Inductively Coupled Plasma Mass Spectrometry and liquid chromatography coupled to tandem mass spectrometry. Aluminum, manganese, strontium, and zinc were the dominant trace elements. All samples complied with EU regulatory limits for toxic metals. More importantly, a wide range of pharmaceutical residues was detected in the supplements. Caffeine was the most frequently found compound, followed by metronidazole, carbamazepine, benzocaine, and tramadol. Particular concern is raised by the calculated TWI (% of tolerable weekly intake) for aluminum. Principal Component Analysis revealed significant compositional differences between Spirulina and Chlorella products, with vanadium notably elevated in conventionally cultivated Spirulina. Surprisingly, no significant differences were observed between organic and conventional products within each algal type. Our findings provide a novel contribution to the field by highlighting the presence of pharmaceutical residues in microalgae-based supplements and addressing a critical knowledge gap concerning potential chronic exposure to these contaminants through dietary intake. Full article

(This article belongs to the Special Issue Metals and Metal Ions in Human Health, Diseases, and Environment)

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24 pages, 823 KB

Open AccessReview

Maternal–Fetal Exposure to Oncoelements and Their Oxidative and Epigenetic Impact on Pregnancy Outcomes

by Joanna Grzesik-Gąsior, Agnieszka Bień, Katarzyna Zalewska, Michał Nieszporek, Katarzyna Witkowska and Anna Merklinger-Gruchała

Int. J. Mol. Sci. 2026, 27(2), 669; https://doi.org/10.3390/ijms27020669 - 9 Jan 2026

Cited by 1 | Viewed by 984

Abstract

The proper course of pregnancy and fetal development depends, among other factors, on maintaining adequate levels of micronutrients in the maternal body. This integrative, concept-driven narrative review summarizes the current state of knowledge on the impact of selected elements, referred to as oncoelements, on placental function and obstetric outcomes. These include both potentially protective elements (selenium, zinc, copper) and toxic metals (cadmium, lead, arsenic), which, in excess may disrupt oxidative, hormonal, and epigenetic homeostasis. Rather than providing a quantitative synthesis, the article is structured around a four-level conceptual model integrating molecular mechanisms, placental protection, clinical outcomes, and umbilical cord blood as a biomarker of prenatal exposure. Mechanisms of toxicity include oxidative stress, mitochondrial dysfunction, DNA damage, and altered gene expression. Given the observational nature of most studies, clinical recommendations remain cautious. Micronutrient assessment may be useful in selected high-risk groups, but requires further validation. In environmentally burdened regions, screening for toxic metals may be considered. Future research should clarify dose–response relationships, define threshold concentrations, and explore molecular biomarkers of exposure. Umbilical cord blood offers a promising matrix for assessing fetal exposure, although interpretation is limited by methodological variability and the lack of reference values. Full article

(This article belongs to the Special Issue Metals and Metal Ions in Human Health, Diseases, and Environment)

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